June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Iron Status and Retinopathy of Prematurity Outcomes among Infants in the Preterm Erythropoietin Neuroprotection Trial (PENUT Trial)
Author Affiliations & Notes
  • Ellen Coley Ingolfsland
    Pediatrics, University of Minnesota Academic Health Center, Minneapolis, Minnesota, United States
  • Nathan Rubin
    Clinical & Translational Science Institute, University of Minnesota Academic Health Center, Minneapolis, Minnesota, United States
  • Raghavendra B Rao
    Pediatrics, University of Minnesota Academic Health Center, Minneapolis, Minnesota, United States
  • Footnotes
    Commercial Relationships   Ellen Ingolfsland None; Nathan Rubin None; Raghavendra Rao None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4175 – F0235. doi:
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      Ellen Coley Ingolfsland, Nathan Rubin, Raghavendra B Rao; Iron Status and Retinopathy of Prematurity Outcomes among Infants in the Preterm Erythropoietin Neuroprotection Trial (PENUT Trial). Invest. Ophthalmol. Vis. Sci. 2022;63(7):4175 – F0235.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To determine the impact of iron status on short- and long-term ROP outcomes among extremely preterm infants (<28 wk gestation) enrolled in the randomized trial of erythropoietin (EPO) or placebo (PENUT Trial). We hypothesized that infants with evidence of low or high iron status would have more severe ROP compared with those with normal iron status.

Methods : A post-hoc analysis of archived NINDS data from the PENUT trial was conducted. Baseline characteristics, iron status (defined as low when serum ferritin (SF, ng/mL) was ≤ 75 or zinc protoporphyrin to heme ratio (ZnPP/H) > 184, normal when SF 75-400 or ZnPP/H 30-183, or high when SF > 400) at 14, 28 and 42 days and 36 wk corrected gestational age (CGA), ROP outcomes (any ROP, ROP stage ≥ 2, ROP requiring treatment, retinal detachment, glasses and strabismus), growth rates, infection rates, hematocrit (hct) and inflammatory biomarker data were reviewed. Association with ROP was analyzed with Chi-squared tests (iron status) and analysis of variance (continuous variables) (significance set at p < 0.05).

Results : 940 infants (mean gestation 25.9 wk; mean birth weight 799 g) were included in the analysis. 51% received EPO. Any stage ROP occurred in in 398 infants (59%), ROP stage ≥ 2 in 229 (34%), and ROP requiring treatment occurred in 47 (7.1%). In unadjusted analysis, there was an association between higher iron status at 14, 28 and 42 days, but not at 36 wk CGA, with any ROP, ROP stage ≥ 2, and ROP requiring treatment. Table 1 summarizes associations between iron status and ROP requiring treatment. Higher IL-6, IL-8, IL-10 and EPO levels on day 14 were associated with ROP requiring treatment. Iron status at 14, 28, and 42 days was associated with EPO administration, delayed cord clamping, rate of weight gain, number of infections from day 0-14 and 14-42 and mean hct wk 1 and wk 2.

Conclusions : Severe ROP may be impacted by systemic iron status. Association with higher iron status on univariate analysis may be explained by pending analyses of timing and dosing of iron supplementation, RBC transfusions and hematocrits. As management of iron status through these means is highly controlled by the clinician, determining this association may have important clinical implications to reduce severe ROP.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Table 1. Association between postnatal iron status and ROP requiring treatment. CGA= corrected gestational age

Table 1. Association between postnatal iron status and ROP requiring treatment. CGA= corrected gestational age

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